rs2075520

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001376232.1(ZP2):c.107G>T(p.Gly36Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,613,558 control chromosomes in the GnomAD database, including 82,393 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 13043 hom., cov: 31)

Exomes 𝑓: 0.30 ( 69350 hom. )

Consequence

ZP2
NM_001376232.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.652

Publications

33 publications found

Variant links:

Genes affected

ZP2 (HGNC:13188): (zona pellucida glycoprotein 2) The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed of three glycoproteins with various functions during fertilization and preimplantation development. The glycosylated mature peptide is one of the structural components of the zona pellucida and functions in secondary binding and penetration of acrosome-reacted spermatozoa. Female mice lacking this gene do not form a stable zona matrix and are sterile. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ZP2 Gene-Disease associations (from GenCC):

oocyte maturation defect 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
inherited oocyte maturation defect
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
female infertility due to zona pellucida defect
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ZP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.534038E-5).

BP6

Variant 16-21211351-C-A is Benign according to our data. Variant chr16-21211351-C-A is described in ClinVar as Benign. ClinVar VariationId is 3060011.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZP2	NM_001376232.1 link	c.107G>T	p.Gly36Val	missense_variant	Exon 2 of 19	ENST00000574091.6	NP_001363161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ZP2	ENST00000574091.6 link	c.107G>T	p.Gly36Val	missense_variant	Exon 2 of 19	1	NM_001376232.1	ENSP00000458991.2
ZP2	ENST00000574002.1 link	c.107G>T	p.Gly36Val	missense_variant	Exon 3 of 20	1		ENSP00000460971.1
ZP2	ENST00000576162.5 link	n.134G>T		non_coding_transcript_exon_variant	Exon 2 of 9	1
ZP2	ENST00000572752.1 link	n.119G>T		non_coding_transcript_exon_variant	Exon 2 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58506

AN:

151790

Hom.:

13029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.342

GnomAD2 exomes

AF:

0.351

AC:

88217

AN:

251212

AF XY:

0.341

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.299

AC:

436901

AN:

1461648

Hom.:

69350

Cov.:

AF XY:

0.300

AC XY:

217976

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.620

AC:

20771

AN:

33476

American (AMR)

AF:

0.471

AC:

21041

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7493

AN:

26132

East Asian (EAS)

AF:

0.425

AC:

16857

AN:

39696

South Asian (SAS)

AF:

0.371

AC:

31997

AN:

86246

European-Finnish (FIN)

AF:

0.283

AC:

15140

AN:

53416

Middle Eastern (MID)

AF:

0.269

AC:

1552

AN:

5768

European-Non Finnish (NFE)

AF:

0.273

AC:

303247

AN:

1111810

Other (OTH)

AF:

0.311

AC:

18803

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

15804

31607

47411

63214

79018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10422

20844

31266

41688

52110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58566

AN:

151910

Hom.:

13043

Cov.:

AF XY:

0.386

AC XY:

28633

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.609

AC:

25248

AN:

41426

American (AMR)

AF:

0.386

AC:

5878

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3460

East Asian (EAS)

AF:

0.440

AC:

2273

AN:

5166

South Asian (SAS)

AF:

0.355

AC:

1709

AN:

4808

European-Finnish (FIN)

AF:

0.274

AC:

2889

AN:

10548

Middle Eastern (MID)

AF:

0.284

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.273

AC:

18559

AN:

67954

Other (OTH)

AF:

0.340

AC:

719

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1705

3410

5115

6820

8525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.310

Hom.:

30501

Bravo

AF:

0.406

TwinsUK

AF:

0.276

AC:

1025

ALSPAC

AF:

0.266

AC:

1026

ESP6500AA

AF:

0.609

AC:

2677

ESP6500EA

AF:

0.279

AC:

2398

ExAC

AF:

0.354

AC:

42926

Asia WGS

AF:

0.342

AC:

1194

AN:

3478

EpiCase

AF:

0.275

EpiControl

AF:

0.267

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZP2-related disorder

Benign:1

Jan 05, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.68

(source)

DANN

Benign

0.086

DEOGEN2

Benign

0.030

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00027

MetaRNN

Benign

0.000015

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

N;N

PhyloP100

0.65

PrimateAI

Benign

0.45

Sift4G

Benign

0.72

T;T

Polyphen

0.0

.;B

Vest4

0.11

MPC

0.073

ClinPred

0.0021

GERP RS

2.4

PromoterAI

-0.0076

Neutral

(source)

Varity_R

0.035

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over